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1.
Pancreas ; 48(8): 985-995, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31425484

RESUMO

Current evidence on cigarette smoking associated with pancreatic cancer mortality is limited. We searched MEDLINE, Web of Science, and Embase databases to identify relevant studies published through January 31, 2018. A random-effects model was used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 20 studies were retrieved, involving 2,517,623 participants. Of these, more than 15,341 patients with pancreatic cancer died. Compared with never smokers, current (summary HR, 1.56; 95% CI, 1.34-1.83) and former (summary HR, 1.15; 95% CI, 1.06-1.26) smokers had elevated risk of total mortality in patients diagnosed with pancreatic cancer. This effect of cigarette smoking is observed both in the Western regions and the Asia-Pacific regions. This effect of smoking is independent of alcohol use, body mass index, and history of diabetes but is modified by tumor stage and study settings. Dose-response associations between smoking and pancreatic cancer mortality were revealed for smoking intensity, cumulative amount of cigarettes smoked, and duration of smoking. Cigarette smoking was associated with an increase in total mortality for patients with pancreatic cancer. Future studies should further clarify the role of smoking as an effect modifier in treatment trials of pancreatic cancer.

2.
BMC Gastroenterol ; 19(1): 145, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420025

RESUMO

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

3.
Surg Endosc ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376008

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in Billroth II anatomy patients is still a technical challenge and factors affecting stone extraction have not yet been clarified. This study aimed to analyze our experience and evaluate potential factors affecting CBD stone extraction. METHODS: A retrospective analysis of CBD stones patients with a history of Billroth II gastrectomy, who underwent therapeutic ERCP for stone extraction at our center from August 1999 to December 2017, was conducted. The outcomes of ERCP and potential factors affecting stone extraction were examined. RESULTS: A total of 227 patients were enrolled, and 176 patients (77.5%) achieved technical success. The success rate of duodenal ampullary access and selective biliary cannulation was 84.1% (191/227) and 92.1% (176/191), respectively. The mean CBD diameter was 15 mm (range 6-35 mm), and the largest stone size was 13 mm (range 4-36 mm). CBD stones were ultimately removed in 137 patients (77.8%), and 105 patients (59.7%) for the first session. Mechanical lithotripsy was used in 17 patients (9.7%). The overall ERCP-related complication rate was 6.3% (11/176), including bleeding in 3 patients (1.7%) and mild pancreatitis in 6 patients (3.4%). The multivariate analysis indicated that CBD stone number ≥ 2 (OR 2.171; 95% CI 1.095-4.306; p = 0.027), and the largest CBD stone size ≥ 12 mm (OR 3.646; 95% CI 1.833-7.251; p < 0.001) were patient-related risk factors for failed stone removal; while the use of endoscopic papillary (large) balloon dilation (EPBD/EPLBD) (OR 0.291; 95% CI 0.147-0.576; p < 0.001) was a procedure-related protective factor for successful stone extraction. CONCLUSIONS: ERCP is safe and effective for extraction of CBD stones in Billroth II anatomy patients. The number and the largest size of CBD stones, and the use of EPBD/EPLBD are predictive factors for CBD stone extraction.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31187782

RESUMO

Background/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II gastrectomy patients is technically demanding and factors affecting its technical difficulty have not yet been clarified. This study aimed to investigate the outcomes of ERCP in Billroth II gastrectomy patients and identify potential factors affecting its technical failure. Patients and Methods: A large retrospective study of 308 consecutive patients (391 procedures) with Billroth II gastrectomy-who underwent ERCP from January 2002 to December 2016-was conducted. The outcomes of ERCP and potential factors affecting its technical failure were analyzed. Results: The success rate of duodenal ampullary access, selective duct cannulation and the accomplishment of expected procedures was 81.3% (318/391), 86.5% (275/318) and 97.3% (256/263), respectively, and the technical success rate was 70.3% (275/391). The overall ERCP-related complication rate was 15.3% (60/391). The multivariate analysis indicated that first-time ERCP attempt [odds ratio (OR) 4.29, 95% confidence interval (CI) 2.34-7.85, P < 0.001], Braun anastomosis (OR 3.65, 95% CI 1.38-9.64, P < 0.009), and no cap-assisted gastroscope (OR 3.05, 95% CI 1.69-5.51, P < 0.001) were significantly associated with technical failure. Conclusions: ERCP is safe, effective and feasible for Billroth II gastrectomy patients. Previous ERCP history, absence of Braun anastomosis and the use of a cap-assisted gastroscope are the predictive factors for its technical success.

5.
Int J Nanomedicine ; 14: 3893-3909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239663

RESUMO

Background: Photothermal and chemotherapy treatment has been frequently studied for cancer therapy; however, chemotherapy is equally toxic to both normal and cancer cells. The clinical application value of most kinds of photothermal transforming agents remains limited, due to their poor degradation and minimal accumulation in tumors. Materials and methods: We reported the synthesis of photothermal transforming agents (MoS2) and chemotherapeutic (doxorubicin, DOX) co-loaded electrospun nanofibers using blend electrospinning for the treatment of postoperative tumor recurrence. Results: Under the irradiation of an 808 nm laser, the as-prepared chitosan/polyvinyl alcohol/MoS2/DOX nanofibers showed an admirable photothermal conversion capability with a photothermal conversion efficiency of 23.2%. These composite nanofibers are in vitro and in vivo biocompatible. In addition, they could control the sustained release of DOX and the generated heat can sensitize the chemotherapeutic efficacy of DOX via enhancing its release rate. Their chemo-/photothermal combined therapy efficiency was systematically studied in vitro and in vivo. Instead of circulating with the body fluid, MoS2 was trapped by the nanofibrous matrix in the tumor and so its tumor-killing ability was not compromised, thus rendering this composite nanofiber a promising alternative for future clinical translation within biomedical application fields. Conclusion: Chitosan/polyvinyl alcohol/MoS2/DOX nanofibers showed an excellent photothermal conversion capability with a photothermal conversion efficiency of 23.2% and can completely inhibit the postoperative tumor reoccurrence.


Assuntos
Dissulfetos/química , Doxorrubicina/uso terapêutico , Molibdênio/química , Nanofibras/química , Nanotecnologia/métodos , Neoplasias/terapia , Fototerapia , Animais , Materiais Biocompatíveis/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HT29 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanofibras/ultraestrutura , Recidiva Local de Neoplasia/patologia , Neoplasias/sangue , Neoplasias/patologia , Neoplasias/cirurgia , Padrões de Referência , Resultado do Tratamento
6.
Theranostics ; 9(10): 2843-2855, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244927

RESUMO

The overproduction of reactive oxygen species (ROS) is linked to inflammatory bowel disease (IBD) and causes oxidative damage to DNA, proteins, and lipids. These ROS promote the initiation and progression of ulcerative colitis (UC). This study proposes a unique concept of nanomaterials with intrinsic enzyme-like activity (nanozymes) to mediate catalytic nanotherapy for IBD. Methods: We first synthesized manganese Prussian blue nanozymes (MPBZs) with multi-enzyme activity. A dextran sulfate sodium (DSS)-induced mouse model of colitis was built. The ROS scavenging capacity and anti-inflammatory effects of the MPBZs were investigated. Results: As a proof of concept, MPBZs with multi-enzyme activity were constructed of variable valence elements (Mn and Fe) via a facile and efficient strategy. Due to the increased intestinal permeability and positively charged surfaces of inflamed mucosa in murine colitis, the prepared MPBZs with nanoscale sizes and negative charges preferentially accumulated at inflamed sites after oral administration. Importantly, MPBZs mediated catalytic nanotherapy for IBD in mice via a primary effect on the toll-like receptor signaling pathway without adverse side effects. Conclusion: MPBZs with multi-enzyme activity were constructed to treat IBD. This nanozyme-based approach is a promising strategy for catalytic nanotherapy in patients with colonic IBD.

7.
Transl Oncol ; 12(9): 1147-1154, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31203147

RESUMO

The bidirectional interaction between pancreatic cancer (PanCa) and diabetes has been confirmed by epidemiological studies, but until now, the underlying molecular mechanisms for this connection is not fully understood yet. Here, we analyzed the clinical and genomic data of 26 pancreatic ductal adenocarcinoma (PDAC) patients without diabetes, and six diabetic PDAC patients, whose tumors underwent targeted next-generation sequencing (551 cancer-related genes included). Ingenuity Pathway Analysis (IPA) was performed to investigate genetic alterations and biological consequences associated with PDACs with or without diabetes. We identified 345 somatic mutations of 153 genes in test cohort and a positive association between diabetes duration and somatic mutation burden. KRAS, TP53, and SMAD4 were the top3 commonly mutated genes at a similar frequency compared to the Cancer Genome Atlas (TCGA) data. Several novel but infrequent mutations in other genes (MDC1, PRB2, and PRB4) were also found. Besides, 13 mutated genes (PIK3CD, SNCAIP, IRF4, HLA-A, NOTCH4, PIM1, ETV6, B2M, CD70, PRDM14, TGFBR1, FLT1, and PARP2) were uniquely found in the diabetic group, mainly involved in immune-related pathways. Further targeted sequencing of these genes in an independent validation cohort (n = 50) revealed significant enrichment in the diabetic group (n = 18, P = 2.6964E-08). Long-standing diabetes (≥3-year duration) may induce increasing somatic mutations with time, facilitating tumor initiation. Gene mutants associated with immune-related pathways could be used to distinguish the diabetic PDAC patients from the non-diabetic cases and allow more selective treatment.

8.
Gastrointest Endosc ; 89(6): 1193-1201.e1, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30660634

RESUMO

BACKGROUND AND AIMS: Colonoscopy insertion is painful for some patients and is one of the main barriers to screening colonoscopy. Few studies have assessed the impact of the supine position (SP) on colonoscopy insertion, especially for unsedated patients. The aim of this randomized controlled trial was to clarify this issue. METHODS: Unsedated patients were randomized to SP or left horizontal position (LHP) as the starting position of colonoscopy insertion. The primary outcome measure was cecal intubation time (CIT), and the secondary outcome measures were descending colon intubation time (DIT), pain score of patients, difficulty score according to the endoscopist, and patients' acceptance of unsedated colonoscopy. RESULTS: A total of 347 patients were randomized to the SP group (175) or the LHP group (172). The CIT in the SP group was significantly shorter than that in the LHP group (275.0 seconds [interquartile range (IQR), 234.0-328.5 seconds] versus 316.0 seconds [IQR, 261.0-370.0 seconds], P < .001). The DIT was also shorter in the SP group (64.5 seconds [IQR, 52.0-86.3 seconds] versus 74.0 seconds [IQR, 62.0-92.0 seconds], P = .001). Compared with the LHP, the SP had a lower pain score (3.3 versus 3.9, P = .002), a lower difficulty score (3.1 versus 3.7, P < .001), a lower frequency of position change (7.1% versus 38.0%, P < .001), and less need for abdominal compression (39.1% versus 45.5%, P = .02). SP was the only modifiable and independent factor identified to reduce CIT and pain score and improve patients' acceptance of unsedated colonoscopy. CONCLUSIONS: As an economical and convenient method, SP can reduce CIT, ease pain, and improve patients' acceptance of unsedated colonoscopy. (Clinical trial registration number: NCT03289442.).

9.
J Dig Dis ; 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30516330

RESUMO

OBJECTIVE: Methotrexate (MTX) can be used as an alternative for Crohn's disease (CD) patients intolerant to thiopurine. Although some studies have reported the efficacy of MTX administration in treating CD, few studies have included Asian patients. This retrospective study aimed to provide some clues regarding MTX treatment in Chinese CD patients. METHODS: We included 27 patients (>18 years) with CD treated with MTX between 2012 and 2017 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University. MTX was administered at 15 mg or 20 mg intramuscularly once per week. The efficacy and adverse reactions of MTX were recorded and analyzed. RESULTS: Over two years, 13 (48.1%) patients who received intramuscular MTX achieved remission for more than 12 months, whereas 4 (14.8%) patients responded to MTX treatment. Eight patients (29.6%) discontinued MTX due to the adverse events. The mean age of those who maintained remission was significantly lower than that of those who did not (35.62 ± 10.99 years vs 45.43 ± 11.93 years, P < 0.05). CONCLUSIONS: Intramuscular MTX administration is safe and effective for patients from a single center in China at doses of 15 or 20 mg/week and can be an alternative therapy for patients intolerant to thiopurine. Elderly CD patients and patients with normal pretreatment C-reaction protein may have reduced response to MTX.

10.
Artigo em Inglês | MEDLINE | ID: mdl-30430823

RESUMO

Alginate-Ca2+ hydrogel has been used to immobilize photothermal materials as well as chemotherapy drugs at lesion sites to prevent their entry into the bloodstream. However, the alginate-Ca2+ gelation mechanism may result in hardening of the blood vessels due to Ca2+ migration to the lesion site. In this study, a unique and facile one-pot formation of chemotherapeutic (doxorubicin, DOX) and polypyrrole (PPy)-containing alginate hydrogel was designed by introducing Fe3+, which can synchronously induce the polymerization of pyrrole and gelatinization of alginate, into the DOX/pyrrole/alginate solution. The formed composite hydrogel was endowed with superior photothermal conversion properties in both the NIR-I (650-950 nm) and NIR-II (1000-1700 nm) biowindows and light-to-heat conversion efficiency higher than 50%, which enabled effective tumor hyperthermia treatment. Besides, NIR irradiation could be used as a remote controller to trigger the DOX-release due to the heat generation, thus achieving continuous and on-demand tumor chemotherapy. The composite polymer hydrogels exhibited favorable hemo-, cyto-, and histocompatibility, as well as simple and cost-effective preparation and good clinical prospects.

12.
ACS Appl Mater Interfaces ; 10(31): 26108-26117, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30028115

RESUMO

The overproduction of reactive oxygen species (ROS) is central to the progression of inflammatory bowel disease (IBD), which may be the potential therapeutic target. Prussian blue (PB) nanoparticles with good biosafety can act as an artificial nanozyme, effectively scavenging ROS. To date, PB-based nanomaterials have not been developed and utilized for treatment of IBD. In this study, poly(vinylpyrrolidone)-modified Prussian blue (PPB) nanoparticles are constructed with good physiological stability and biosafety by a simple and efficient method. The prepared PPBs with capabilities of scavenging ROS and inhibiting proinflammatory cytokine significantly reduce colitis in mice without distinct side effects via intravenous administration. This report provides a demonstration of the protective effect of PB-based nanomedicine against IBD in living animals, offering hope and a potential alternative treatment option for patients suffering from IBD.

13.
J Gastroenterol Hepatol ; 33(10): 1722-1727, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29575167

RESUMO

BACKGROUND AND AIM: Empirical proton pump inhibitor (PPI) treatment is recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD) and as a therapy for symptomatic control, with responses generally seen within 4 weeks. However, there are no real-world data assessing the effectiveness of short-term empirical treatment with PPIs in patients with GERD in China. METHODS: The ENLIGHT study was a multicenter, prospective, observational study conducted in China. The primary outcome was the overall response rate after 4 weeks' empirical treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a gastroesophageal reflux disease questionnaire score of ≥ 8, prescribed empirical PPI treatment by their physicians and with no planned endoscopy were eligible to participate. Statistical analyses were primarily descriptive. RESULTS: Overall, 987 patients were eligible to participate and were included in the full analysis set (FAS); 707 patients were included in the per protocol set. In the FAS, esomeprazole was received by 57.1% of patients and was the most commonly used PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%) of patients were considered responders to PPI. The response rate at the end of 2-week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the per protocol set were similar to those of the FAS. CONCLUSIONS: Short-term empirical PPI treatment can provide an effective relief of GERD symptoms in most Chinese patients in real-world practice.


Assuntos
Esomeprazol/administração & dosagem , Esomeprazol/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Pacientes Ambulatoriais , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Pantoprazol , Estudos Prospectivos , Rabeprazol/administração & dosagem , Rabeprazol/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
ACS Appl Mater Interfaces ; 10(4): 3392-3404, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-29313334

RESUMO

The objective of the present study was to construct an alginate (AG)-based phase-changeable and injectable hydrogel for imaging-guided tumor hyperthermia and chemotherapy. Based on the binding between the α-l-guluronic blocks of AG and calcium ions, the AG/MoS2/Bi2S3-poly(ethylene glycol) (MBP)/doxorubicin (DOX) solution formed a cross-linked hydrogel to simultaneously encapsulate MBP nanosheets and DOX within the hydrogel matrix. The in situ formed hydrogel can act as a reservoir to control the release of entrapped drug molecules, and the doped MBP nanosheets and DOX can realize computed tomography/photoacoustic dual-modal imaging-guided in vivo tumor photothermal therapy and chemotherapy, respectively. The AG/MBP/DOX hydrogel exhibited excellent photothermal conversion properties with mass extinction coefficient of 45.1 L/g/cm and photothermal conversion efficiency of 42.7%. Besides, the heat from the photothermal transformation of MBP can promote drug diffusion from the hydrogel to realize on-demand drug release. Additionally, the hydrogel system can restrain MBP and DOX from entering into the blood stream during therapy, and therefore substantially decrease their side effects on normal organs. More importantly, the drug loading of the AG hydrogel was general and can be extended to the encapsulation of antibiotics, such as amoxicillin, for the prevention of postoperative infections.

15.
Trials ; 18(1): 513, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29096689

RESUMO

BACKGROUND: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis. METHODS/DESIGN: The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications. DISCUSSION: The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Cálculos/terapia , Indometacina/administração & dosagem , Litotripsia/efeitos adversos , Pancreatite Crônica/terapia , Pancreatite/prevenção & controle , Administração Retal , Anti-Inflamatórios não Esteroides/efeitos adversos , Cálculos/diagnóstico , China , Protocolos Clínicos , Método Duplo-Cego , Humanos , Indometacina/efeitos adversos , Pancreatite/diagnóstico , Pancreatite/etiologia , Pancreatite Crônica/diagnóstico , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
16.
Acta Biomater ; 58: 442-454, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28611005

RESUMO

Two-dimensional transition metal dichalcogenides (TMDs) have been receiving great attention as NIR photothermal transducing agent in tumor photothermal therapy. Keeping in mind the low efficiency of the conventional top-down exfoliated 2D TMDs and the complexity of their surface modifications, we herein proposed a bottom-up strategy for the one-pot hydrothermal and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets. The material design was based on the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten. The WS2 nanosheets with synchronous surface PVP grafting showed an excellent photothermal conversion performance, while the surface anchored PVP guaranteed its colloidal stability. Moreover, the strong X-ray attenuation ability and near-infrared (NIR) absorbance of WS2-PVP360kDa enabled the sensitive in vitro and in vivo computed tomography and photoacoustic imaging. The WS2-PVP360kDa nanosheets were biocompatible and exhibited promising in vitro and in vivo anti-cancer efficacy. Findings in this report may greatly promote the design of colloidal stable and biocompatible 2D TMDs and their future clinical translations. STATEMENT OF SIGNIFICANCE: A bottom-up strategy for the one-pot and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets was proposed for the first time. By hydrothermally treating the mixture solution of tetrathiotungstate and PVP, Owing to the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten, PVP was synchronously graphed on WS2-PVP nanosheets surface. The formed WS2-PVP nanosheets were colloidal stable, biocompatible, and exhibited promising computed tomography, photoacoustic imaging and tumor photothermal therapy efficacy both in vitro and in vivo.


Assuntos
Nanoestruturas , Neoplasias Experimentais , Sulfetos , Tomografia Computadorizada por Raios X , Compostos de Tungstênio , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Povidona/química , Povidona/farmacologia , Sulfetos/síntese química , Sulfetos/química , Sulfetos/farmacologia , Compostos de Tungstênio/síntese química , Compostos de Tungstênio/química , Compostos de Tungstênio/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Gastroenterol Hepatol ; 32(6): 1152-1159, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28024166

RESUMO

Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.


Assuntos
Inibidores da Bomba de Prótons/administração & dosagem , Ticlopidina/análogos & derivados , 2-Piridinilmetilsulfinilbenzimidazóis , Anticoagulantes/administração & dosagem , Grupo com Ancestrais do Continente Asiático/genética , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel , Citocromo P-450 CYP2C19/genética , Dexlansoprazol , Interações de Medicamentos , Quimioterapia Combinada , Extremo Oriente , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/prevenção & controle , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Isoenzimas , Pantoprazol , Inibidores da Agregação de Plaquetas/administração & dosagem , Polimorfismo Genético , Rabeprazol , Ticlopidina/administração & dosagem
18.
Oncotarget ; 8(63): 106707-106720, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29290983

RESUMO

The two-dimensional molybdenum disulfide (MoS2) nanosheet has been extensively studied as a novel photothermal transducing agent. However, top-down exfoliation to produce MoS2 nanosheets is inefficient, and MoS2 nanosheet surface modification procedures are complex. Here, we report the synchronous synthesis and surface modification of 2D MoS2 nanosheets with a polyvinylpyrrolidone (PVP)-assisted one-pot hydrothermal method. Due to the chelating-coordinating effect between the lone-pair electrons of the PVP carbonyl oxygen and the unoccupied 4d orbitals of molybdenum, the PVP chains could graft onto the surface of MoS2 and guide the growth of the nanosheets. The resultant MoS2-PVP nanosheets were ultra-small (21.4 ± 4.4 nm) and exhibited excellent colloidal stability. Moreover, the strong near-infrared absorption of the MoS2-PVP nanosheets enabled sensitive photothermal conversion performance (with a mass extinction coefficient of 23.33 L g-1 cm-1) and in vitro/in vivo photoacoustic imaging. The MoS2-PVP nanosheets had excellent in vitro and in vivo compatibility and were used for highly efficient tumor photothermal therapy in xenograft tumor-bearing mice. The findings in this report will facilitate the rational design of stable colloidal 2D transition-metal dichalcogenides for effective photothermal cancer therapy.

19.
World J Gastroenterol ; 21(22): 6965-73, 2015 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-26078574

RESUMO

AIM: To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy. METHODS: This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate. RESULTS: Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated. CONCLUSION: Chinese patients diagnosed with chronic gastritis achieved marginally better control of reflux symptoms with an 8-wk vs a 2-wk esomeprazole regimen, with a similar safety profile.


Assuntos
Esomeprazol/administração & dosagem , Gastrite/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Doença Crônica , Esquema de Medicação , Endoscopia Gastrointestinal , Esomeprazol/efeitos adversos , Feminino , Gastrite/diagnóstico , Gastrite/etnologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inibidores da Bomba de Prótons/efeitos adversos , Indução de Remissão , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
20.
Dig Dis Sci ; 60(6): 1716-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25599960

RESUMO

BACKGROUND AND AIM: Population-based endoscopic studies of esophageal eosinophilia and eosinophilic esophagitis are limited in the world. This study was aiming to describe features of esophageal eosinophilia and eosinophilic esophagitis in a representative sample of the adult in Shanghai, China. METHODS: As part of a large epidemiological study, 3,600 individuals (aged 18-80 years) were randomly selected in Shanghai, China. They were asked to undergo endoscopy and have at least four esophageal biopsies taken from 0.5 cm above the Z-line and any abnormal areas. Any eosinophil infiltration of the epithelium was defined as esophageal eosinophilia. Eosinophilic esophagitis was defined as ≥15 eosinophils/high-power field in esophageal biopsies. RESULTS: A total of 1,030 individuals accepted to have endoscopy and 1,021 individuals with biopsy results were suitable for analysis. Esophageal eosinophilia was present in 67 subjects (6.6 %). Eosinophilic esophagitis was present in four cases (0.4 %). No significant association was found between the presence of esophageal eosinophilia and reflux esophagitis, Barrett's esophagus, symptom-defined gastroesophageal reflux disease or H. pylori infection. Most individuals with esophageal eosinophilia (80.6 %) did not have any of the upper gastrointestinal symptoms. CONCLUSIONS: Esophageal eosinophilia was present in nearly 6.6 % of the general adult population of China; 0.4 % had eosinophilic esophagitis. Most of individuals with esophageal eosinophilia were asymptomatic.


Assuntos
Esofagite Eosinofílica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , China/epidemiologia , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários
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